Effect of bethanechol, gastrin I, or cholecystokinin on myoelectrical activity.

1979 ◽  
Vol 236 (4) ◽  
pp. E458
Author(s):  
W J Snape ◽  
S Cohen

The purpose of this study was to determine the effect of bethanechol, gastrin I, or the octapeptide of cholecystokinin (CCK-OP) on the smooth muscle of the isolated cat colon. Myoelectrical activity was recorded with monopolar glass-pore electrodes. Slow-wave frequency was 5.9 +/- 0.2 cycles/min during the basal period. Slow waves were generally coupled during the control period and the apparent propagation velocity was predominantly aborad at a velocity of 3.8 +/- 0.4 mm/s. Spike activity was superimposed on 11.9 +/- 1.5% of the slow waves during the control period. Bethanechol stimulated a dose-dependent increase in colonic spike activity, with a threshold concentration of 10(-7) M. Bethanechol did not alter the congruence of the colonic slow-wave frequency at any concentration. Gastrin I or CCK-OP increased colonic spike activity. The threshold concentrations for gastrin I and CCK-OP were 2 X 10(-11) M and 4 x 10(-11) M, respectively. Unlike bethanechol, gastrin I (2 X 10(-9) M - 2 X 10(-8) M) and CCK-OP (4 X 10(-9) - 4 X 10(-8) M) altered slow-wave frequency and decreased slow-wave congruence. These studies suggest that 1) bethanechol, gastrin I, or CCK-OP increases colonic spike activity, and 2) only gastrin I or CCK-OP alters the slow-wave frequency of colonic muscle. Thus neurohumoral substances may act independently on colonic spike activity and colonic slow-wave frequency.

1999 ◽  
Vol 276 (2) ◽  
pp. G518-G528 ◽  
Author(s):  
S.-M. Huang ◽  
S. Nakayama ◽  
S. Iino ◽  
T. Tomita

In circular muscle preparations isolated from the guinea pig gastric antrum, regular spontaneous electrical activity (slow waves) was recorded. Under normal conditions (6 mM K+), the frequency and shape of the slow waves were similar to those observed in ordinary stomach smooth muscle preparations. When the resting membrane potential was hyperpolarized and depolarized by changing the extracellular K+ concentration (2–18 mM), the frequency of slow waves decreased and increased, respectively. Application of cromakalim hyperpolarized the cell membrane and reduced the frequency of slow waves in a dose-dependent manner. Cromakalim (3 μM) hyperpolarized the membrane, and slow waves ceased in most preparations. In the presence of cromakalim, subsequent increases in the extracellular K+ concentration restored the frequency of slow waves accompanied by depolarization. Also, glibenclamide completely antagonized this effect of cromakalim. In smooth muscle strips containing both circular and longitudinal muscle layers, such changes in the slow wave frequency were not observed. It was concluded that the maneuver of isolating circular smooth muscle altered the voltage dependence of the slow wave frequency.


1980 ◽  
Vol 238 (4) ◽  
pp. G321-G325 ◽  
Author(s):  
W. J. Snape ◽  
S. Shiff ◽  
S. Cohen

The purpose of the study was to determine the effect of the bile salt, deoxycholic acid, on colonic myoelectrical and contractile activity recorded from a loop of proximal colon in the anesthetized rabbit. Myoelectrical activity was recorded from bipolar electrodes attached to the serosal surface of the proximal colon. Contractile activity of the circular smooth muscle was measured with a strain gauge attached in the circular direction on the serosal surface of the colonic loop. The colonic slow wave frequency was 12.5 +/- 1.1 cycles/min. The slow wave frequency throughout the loop was homogeneous with a low coefficient of variation of the slow wave frequency (5.8 +/- 0.3). There were spike potentials superimposed on 78.1 +/- 3.4% of the slow waves. The addition of 8 or 16 mM deoxycholic acid did not change the slow wave or spike activity. However, deoxycholic acid stimulated a dose-dependent increase in migrating action potential complexes. These complexes were associated with a forceful contraction of the circular smooth muscle that propelled luminal contents in the direction of the burst. Deoxycholic acid also stimulated an increase in luminal fluid content.


1996 ◽  
Vol 271 (6) ◽  
pp. L1014-L1022 ◽  
Author(s):  
R. Rajah ◽  
S. E. Nunn ◽  
D. J. Herrick ◽  
M. M. Grunstein ◽  
P. Cohen

We have previously demonstrated that the asthma-associated proinflammatory eicosanoid leukotriene D4 (LTD4) is comitogenic with insulin-like growth factors (IGF) in airway smooth muscle (ASM) cells. This synergistic effect of LTD4 and IGF on ASM cell growth involves proteolysis of ASM-produced inhibitory IGF-binding proteins (IGFBP). In this report, we analyzed the conditioned media (CM) from LTD4-treated human ASM cells (ASM-LTD4-CM) by Western ligand blotting and demonstrated a marked LTD4-induced reduction in the levels of the intact IGFBP (predominantly IGFBP-2) secreted by these cells. The IGFBP-2 in the ASM-LTD4-CM was identified as lower-molecular-weight fragments by Western immunoblotting. Incubation with 125I-labeled IGFBP demonstrated that an IGFBP protease was induced in the ASM cells in response to LTD4 treatment. Immunodepletion of ASM-LTD4-CM with anti-matrix metalloproteinase (MMP)-1 antibodies demonstrated a dose-dependent reduction of IGFBP proteolysis. Tissue inhibitor of MMP-1 and Batimastat (synthetic) inhibited proteolysis of IGFBP. Immunoblotting the ASM-LTD4-CM with anti-MMP-1 demonstrated a dose-dependent increase in MMP-1 protein. Similar results were also obtained by immunocytochemistry. Collectively, these observations demonstrate that MMP-1 is an IGFBP protease induced by leukotrienes that plays a significant role in modulating IGF action in ASM cells. A similar mechanism may be applicable in vivo in the airways of patients with asthma.


1991 ◽  
Vol 260 (2) ◽  
pp. C375-C382 ◽  
Author(s):  
J. M. Post ◽  
R. J. Stevens ◽  
K. M. Sanders ◽  
J. R. Hume

The effects of cromakalim (BRL 34915) and its optical isomer lemakalim (BRL 38227) were investigated in intact tissue and freshly dispersed circular muscle cells from canine proximal colon. Cromakalim and lemakalim hyperpolarized resting membrane potential, shortened the duration of slow waves by abolishing the plateau phase, and decreased the frequency of slow waves. Glyburide, a K channel blocker, prevented the effect of cromakalim on slow-wave activity. The mechanisms of these alterations in slow-wave activity were studied in isolated myocytes under voltage-clamp conditions. Cromakalim and lemakalim increased the magnitude of a time-independent outward K current, but cromakalim also reduced the peak outward K current. Glyburide inhibited lemakalim stimulation of the time-independent background current. Nisoldipine also reduced the peak outward current, and in the presence of nisoldipine, cromakalim did not affect the peak outward component of current. This suggested that cromakalim may block a Ca-dependent component of the outward current. Lemakalim did not affect the peak outward current. We tested whether the effects of cromakalim on outward current might be indirect due to an effect on inward Ca current. Cromakalim, but not lemakalim, was found to inhibit L-type Ca channels; however, glyburide did not alter cromakalim inhibition of inward Ca current. We conclude that the effects of cromakalim and lemakalim on membrane potential and slow waves in colonic smooth muscle appear to result primarily from stimulation of a time-independent background K conductance. The effects of these compounds on channel activity may explain the inhibitory effect of these compounds on contractile activity.


1975 ◽  
Vol 229 (2) ◽  
pp. 484-488 ◽  
Author(s):  
AK Mukhopadhyay ◽  
LR Johnson ◽  
EM Copeland ◽  
NW Weisbrodt

The effect of intravenously administered secretin (0.5, 2.0, 6.0 U/kg-h) and intraduodenal acidification (13.2 meq/h HCl) on the electrical activity of the small bowel of three conscious dogs with gastric and duodenal cannulas was observed. Electrical activity was recorded in fasted as well as fed conditions through silver wire electrodes implanted along the entire length of the small bowel. Intravenous infusion of secretin in all dosages and in all dogs delayed the onset of the interdigestive myoelectric complex and reduced the total percentage of slow waves with superimposed spike potentials. Intraduodenal acidification also inhibited the interdigestive myoelectric complex, which developed incompletely with fewer action potentials on slow waves. Secretin did not produce any alteration in the fed pattern of activity, slow-wave frequency, or the caudal migration of the interdigestive myoelectric complex. The present study indicates that the nuerohumoral mechanisms responsible for initiation of the interdigestive myoelectric complex may be different from those responsible for its caudal migration.


1978 ◽  
Vol 235 (3) ◽  
pp. E249 ◽  
Author(s):  
P Thor ◽  
R Król ◽  
S J Konturek ◽  
D H Coy ◽  
A V Schally

Somatostatin, a growth hormone-release inhibiting hormone, has been found to be a powerful inhibitor of gastric and pancreatic secretion as well as of hormone release in the digestive system. This study was undertaken to determine the influence of somatostatin on the myoelectrical activity pattern of the small bowel. Three conscious dogs were prepared with electrodes spaced 25 cm apart along the entire small intestine. Intravenous infusions of somatostatin were administered in various doses (0.6--5.0 microgram/kg.h) while spike activity and slow waves were recorded under fasting conditions, after a meat meal, or during intravenous infusion of gastrin, caerulein, or insulin. Somatostatin at a dose of 0.6 microgram/kg.h almost doubled the frequency of the interdigestive myoelectric complex. Somatostatin in fed dogs caused a dose-dependent decrease of the normal fed spike activity, and at higher doses it induced a pattern like that seen in fasting animals. The slow-wave frequency in both fasted and fed conditions was not changed significantly. We conclude that somatostatin given under basal conditions increases the frequency of the interdigestive complex and, when administered after feeding, converts the fed-type pattern to the fasted-type pattern. It may therefore play a promoting role in initiating the interdigestive myoelectric complex.


2009 ◽  
Vol 296 (6) ◽  
pp. G1180-G1190 ◽  
Author(s):  
Abigail S. Forrest ◽  
Grant W. Hennig ◽  
Sari Jokela-Willis ◽  
Chong Doo Park ◽  
Kenton M. Sanders

Gastric emptying depends on functional coupling of slow waves between the corpus and antrum, to allow slow waves initiated in the gastric corpus to propagate to the pyloric sphincter and generate gastric peristalsis. Functional coupling depends on a frequency gradient where slow waves are generated at higher frequency in the corpus and drive the activity of distal pacemakers. Simultaneous intracellular recording from corpus and antrum was used to characterize the effects of PGE2 on slow waves in the murine stomach. PGE2 increased slow-wave frequency, and this effect was mimicked by EP3, but not by EP2, receptor agonists. Chronotropic effects were due to EP3 receptors expressed by intramuscular interstitial cells of Cajal because these effects were not observed in W/W V mice. Although the integrated chronotropic effects of EP3 receptor agonists were deduced from electrophysiological experiments, no clear evidence of functional uncoupling was observed with two-point electrical recording. Gastric peristalsis was also monitored by video imaging and spatiotemporal maps to study the impact of chronotropic agonists on propagating contractions. EP3 receptor agonists increased the frequency of peristaltic contractions and caused ectopic sites of origin and collisions of peristaltic waves. The impact of selective regional application of chronotropic agonists was investigated by use of a partitioned bath. Antral slow waves followed enhanced frequencies induced by stimulation of the corpus, and corpus slow waves followed when slow-wave frequency was elevated in the antrum. This demonstrated reversal of slow-wave propagation with selective antral chronotropic stimulation. These studies demonstrate the impact of chronotropic agonists on regional intrinsic pacemaker frequency and integrated gastric peristalsis.


1987 ◽  
Vol 252 (5) ◽  
pp. G654-G661
Author(s):  
W. J. Snape ◽  
S. T. Tan ◽  
H. W. Kao

The aim of this study is to compare the action of the cholinergic agonist, bethanechol, with the action of the octapeptide of cholecystokinin (CCK-OP) on feline circular colonic smooth muscle membrane potential and isometric tension, using the double sucrose gap. Depolarization of the membrane greater than 10 mV by K+ or bethanechol increased tension and spontaneous spike activity. CCK-OP (10(-9) M) depolarized the membrane (6.1 +/- 1.3 mV) without an increase in tension or spike activity. Depolarization of the membrane by increasing [K+]o was associated with a decrease in the membrane resistance. The slow-wave duration (2.3 +/- 0.2 s) was unchanged by administration of K+ or bethanechol but was prolonged after increasing concentrations of CCK-OP. The maximum effect occurred at a 10(-10) M concentration of CCK-OP (4.5 +/- 0.4 s, P less than 0.01). At higher concentrations of CCK-OP (greater than 10(-10) M), the slow-wave pattern became disorganized. Addition of increasing concentrations of [K+]o or bethanechol, but not CCK-OP, stimulated a concentration-dependent increase in the maximum rate of rise (dV/dtmax) of an evoked spike potential. These studies suggest 1) bethanechol decreased the membrane potential without altering the slow-wave activity, whereas CCK-OP has a minimal effect on the membrane potential but distorted the slow-wave shape; 2) an increased amplitude of the spike and dV/dtmax of the spike were associated with an increase in phasic contractions after bethanechol or increased [K+]o; 3) the lack of an increase in the spike amplitude and the dV/dtmax to CCK-OP was associated with no increase in phasic contraction.


1994 ◽  
Vol 266 (3) ◽  
pp. G485-G496 ◽  
Author(s):  
L. W. Liu ◽  
L. Thuneberg ◽  
J. D. Huizinga

Incubation with 50 microM methylene blue (MB) and subsequent intense illumination resulted in abolition of the slow-wave activity in the submuscular interstitial cells of Cajal-circular muscle (ICC-CM) preparations of canine colon. This was often accompanied by a decrease in resting membrane potential. Repolarization of cells back to -70 mV did not restore the slow-wave activity, indicating that MB plus light directly interrupted the generation mechanism of slow waves. After MB incubation, a 2-min illumination consistently changed the mitochondrial conformation in ICCs from very condensed to orthodox, without inducing any obvious changes in smooth muscle cells. After 4- to 10-min illumination, ICCs became progressively more damaged with swollen and ruptured mitochondria, loss of cytoplasmic contrast and detail, loss of caveolae, and rupture of the plasma membrane. No damage was seen in smooth muscle cells or nerves. Gap junctional ultrastructure was preserved. Intense illumination without preincubation with MB left the slow waves and the ultrastructure of ICC-CM preparations unaffected. In CM preparations, without the submuscular ICC-smooth-muscle network, MB plus light induced no changes in electrical activity. We conclude that the correlation between selective damage to the submuscular ICCs (relative to smooth muscle) and selective loss of the slow-wave activity (relative to other electrical activity of the CM) strongly indicates that the ICCs play an essential role in the generation of slow waves.


1988 ◽  
Vol 66 (9) ◽  
pp. 1161-1165 ◽  
Author(s):  
Beverley Greenwood ◽  
Jan D. Huizinga ◽  
Edwin Chow ◽  
Wylie J. Dodds

The relationship between transmural potential difference (PD) and smooth muscle electrical and mechanical activity was investigated in the rabbit ileum in vitro. Transmural PD was monitored using agar salt bridge electrodes connected via calomel half cells to an electrometer. Force displacement transducers recorded predominantly longitudinal smooth muscle activity. Concurrently, predominantly circular muscle activity was recorded at three sites using intraluminal pressure probes. At the same sites, suction electrodes monitored electrical activity of the smooth muscle. In all experiments, fluctuations in transmural PD were temporally linked to smooth muscle mechanical and electrical activity. The frequency of PD oscillations, electrical slow waves, and cyclic pressure changes were identical within each segment. Adrenaline abolished smooth muscle electrical spiking, all mechanical activity, and transmural fluctuations in PD. However, the slow waves were not abolished, though their frequency was increased. Phentolamine but not propranolol reversed the effects of adrenaline, thus slow wave frequency is influenced by α-adrenergic stimulation in the rabbit ileum. In conclusion, oscillations in transmural PD are unrelated to the ionic processes associated with the slow wave. However, they are in some way linked to smooth muscle contractile activity, possibly via an intrinsic neural mechanism as observed in the guinea pig.


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